Genetic Variant TOMM20L:p.Arg34Gly (chr14-58396057-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_207377.3(TOMM20L):c.100C>G(p.Arg34Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000555 in 1,261,560 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

TOMM20L
NM_207377.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.137

Publications

0 publications found

Variant links:

Genes affected

TOMM20L (HGNC:33752): (translocase of outer mitochondrial membrane 20 like) Predicted to enable mitochondrion targeting sequence binding activity. Predicted to contribute to protein transmembrane transporter activity. Predicted to be involved in protein import into mitochondrial matrix and tRNA import into mitochondrion. Predicted to be integral component of membrane. Predicted to be part of mitochondrial outer membrane translocase complex. Predicted to be integral component of mitochondrial outer membrane. [provided by Alliance of Genome Resources, Apr 2022]

TOMM20L links:

TOMM20L-DT (HGNC:55443): (TOMM20L divergent transcript)

TOMM20L-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207377.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOMM20L	NM_207377.3	MANE Select	c.100C>G	p.Arg34Gly	missense	Exon 1 of 5	NP_997260.1	Q6UXN7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TOMM20L	ENST00000360945.7	TSL:1 MANE Select	c.100C>G	p.Arg34Gly	missense	Exon 1 of 5	ENSP00000354204.2	Q6UXN7
TOMM20L	ENST00000557754.1	TSL:1	n.100C>G		non_coding_transcript_exon	Exon 1 of 4	ENSP00000451683.1	G3V4A4
TOMM20L-DT	ENST00000556390.2	TSL:3	n.-231G>C		upstream_gene	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000278

AC:

AN:

143894

AF XY:

0.0000479

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000357

GnomAD4 exome

AF:

0.00000555

AC:

AN:

1261560

Hom.:

Cov.:

AF XY:

0.0000113

AC XY:

AN XY:

620894

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25658

American (AMR)

AF:

0.00

AC:

AN:

22896

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19586

East Asian (EAS)

AF:

0.00

AC:

AN:

30066

South Asian (SAS)

AF:

0.0000967

AC:

AN:

51714

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45272

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4862

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1011392

Other (OTH)

AF:

0.0000399

AC:

AN:

50114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000174

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.21

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.39

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.77

M_CAP

Pathogenic

0.56

MetaRNN

Uncertain

0.73

MetaSVM

Benign

-0.79

MutationAssessor

Pathogenic

3.0

PhyloP100

0.14

PrimateAI

Pathogenic

0.83

PROVEAN

Pathogenic

-5.8

REVEL

Benign

0.23

Sift

Uncertain

0.0040

Sift4G

Benign

0.14

Polyphen

0.98

Vest4

0.47

MutPred

0.66

Loss of solvent accessibility (P = 0.0159)

MVP

0.35

MPC

1.6

ClinPred

0.58

GERP RS

2.7

PromoterAI

0.50

Over-expression

(source)

Varity_R

0.82

gMVP

0.35

Mutation Taster

=86/14

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over